The genetic variation of the tenomodulin gene (TNMD) is associated with serum levels of systemic immune mediators--the Finnish Diabetes Prevention Study.
We have reported that the genetic variation of the tenomodulin gene (TNMD) is associated with the risk of type 2 diabetes (T2DM), central obesity, and impaired glucose metabolism and the TNMD mRNA levels correlate with serum and mRNA levels of inflammatory markers. Our objective was to investigate the genetic associations of the single nucleotide polymorphisms of the TNMD gene with the serum levels of systemic immune mediators. Seven single nucleotide polymorphisms were genotyped from 507 participants of the Finnish Diabetes Prevention Study. All subjects had body mass index >25 and impaired glucose tolerance. The sequence variation of tenomodulin was consistently associated with the serum concentrations of acute phase reactants, macrophage migration inhibitory factor, and CCR5 receptor ligands. The genotype effects were modified by status of glucose metabolism and central obesity. Markers associated with increased risk of T2DM in our previous study were associated with serum concentrations of acute phase proteins in men so that the subjects possessing the genotypes associated with increased risk of T2DM had higher serum concentrations of acute phase reactants. These results indicate that the genetic variation of TNMD is associated with low-grade inflammation. The putative link between TNMD and T2DM could be mediated through the effects on systemic immune mediators.


Passive rewarming from torpor in hibernating bats: minimizing metabolic costs and cardiac demands.
Endothermic arousal from torpor is an energetically costly process and imposes enormous demands on the cardiovascular system, particularly during early stage arousal from low body temperature (Tb). To minimize these costs many bats and other heterothermic endotherms rewarm passively from torpor using solar radiation or fluctuating ambient temperature (Ta). Because the heart plays a critical role in the arousal process in terms of blood distribution and as a source of heat production, it is desirable to understand how the function of this organ responds to passive rewarming and how this relates to changes in metabolism and Tb. We investigated heart rate (HR) in hibernating long-eared bats (Nyctophilus gouldi) and its relationship to oxygen consumption (V̇o₂) and subcutaneous temperature (Tsub) during exposure to increasing Ta compared with endogenous arousals at constant low Ta. During passive rewarming, HR and V̇o₂ remained low over a large Tsub range and increased concurrently with increasing Ta (Q₁₀ 2.4 and 2.5, respectively). Absolute values were higher than during steady-state torpor but below those measured during torpor entry. During active arousals, mean HR and V̇o₂ were substantially higher than during passive rewarming at corresponding Tsub. In addition, partial passive rewarming reduced the cost of arousal from torpor by 53% compared with entirely active arousal. Our data show that passive rewarming considerably reduces arousal costs and arousal time; we suggest this may also contribute to minimizing exposure to oxidative stresses as well as demands on the cardiovascular system.


Age-related changes in adrenergic alpha 1, alpha 2, and beta receptors of rat white fat cell membranes: an analysis using [3H]bunazosin as a novel ligand for the alpha 1 adrenoceptor.
Age-related changes in alpha 1-, alpha 2-, and beta-catecholamine receptors on membrane of rat epididymal fat cells were investigated. Both young (6 weeks old, weight about 190 g) and aged (20 weeks old, weight about 490 g) Sprague-Dawley male rats were used. For the alpha 1-adrenoceptor binding experiment, we developed a novel analytical method using the hydrophilic alpha 1-receptor selective antagonist, [3H]bunazosin. The binding of [3H]bunazosin to its binding sites was rapid, reversible, saturable, and stereospecific. Scatchard binding analysis showed a single class of binding site. The sites were characterized as alpha 1-adrenoceptors by inhibition experiments using various agonists and antagonists. The number of maximum binding sites (Bmax) of alpha 1-receptor binding was 37.0 +/- 6.5 (young) versus 24.0 +/- 3.2 (aged) fmol/mg protein (P less than 0.01). [3H]Rauwolscine and [3H]CGP-12177 were used for alpha 2- and beta-receptor binding, respectively. In alpha 2-receptor detection using [3H]rauwolscine as a ligand, Bmax increased markedly from 19.8 +/- 4.9 to 86.2 +/- 19.5 fmol/mg protein (P less than 0.01). In contrast, Bmax for beta-receptor decreased from 69.7 +/- 9.7 to 45.4 +/- 13.9 fmol/mg protein with increasing rat age (P less than 0.05). Kd showed no change in each of the binding experiments between young and aged rats. The cell volume increased from 0.07 +/- 0.02 to 0.15 +/- 0.06 nl. It is implied that anti-lipolytic activity strengthened on the whole mainly with the marked increase of alpha 2-receptor number and decrease of beta-receptor number.(ABSTRACT TRUNCATED AT 250 WORDS)


Determination of cytosol c-erbB-2 protein in breast cancer by sandwich enzyme immunoassay.
We determined cytosol c-erbB-2 protein levels using a sandwich enzyme immunoassay in benign breast disease and primary and recurrent breast cancer and analyzed the relationship between c-erbB-2 protein levels and clinicopathological factors. Overexpression of c-erbB-2 protein, the cut-off value being set at 18 ng/mg protein, was observed in 26 of the 139 cases of stages I-IIIB breast cancer (18.7%), four of the 12 cases of stage IV breast cancer (33.3%) and seven of the 13 recurrent breast cancer cases (53.8%). The levels of c-erbB-2 protein were significantly different between the stages. Overexpression of c-erbB-2 protein in stages I-IIIB breast cancer was associated with histological grade and serum CEA level, but not with other clinicopathological factors. In addition, there was an inverse correlation in the group of stages I-III plus IV breast cancer between c-erbB-2 protein expression and estrogen receptor status. Overexpression of c-erbB-2 protein can be easily determined in the cytosol fraction together with hormonal receptor by this method. The prognostic importance will be evaluated in ongoing adjuvant trials for operable breast cancer patients.


Pediatric intracranial ependymomas: prognostic relevance of histological, immunohistochemical, and flow cytometric factors.
The correlation between the histological features and clinical outcome remains poor in pediatric intracranial ependymomas. We performed a retrospective study of a group of 31 patients (diagnosed from 1985 to 1995) to assess prognostic implications of the current grading system, of histological and immunohistochemical features, and of ploidy status estimated by flow cytometry. Immunoexpression of a broad spectrum of antigens was evaluated, including MIB-1, topoisomerase-IIalpha, cyclin D1, glial and epithelial proteins (GFAP, EMA, cytokeratins), molecules involved in controlling apoptosis (bcl-2, caspase-3/CPP32), and p53 oncoprotein. Univariate and multivariate statistical analyses were performed to evaluate the influence of each variable on both the progression free survival (PFS) and the overall survival (OS) with at least 7-year follow up. Although we showed a significant correlation between histological grade and prognosis, the current grading system failed in predicting outcome in nearly one third of individual cases. Problems with interpathologist reproducibility were also demonstrated. The extent of surgical resection was the only clinical factor that was associated with survival. Both the PFS and the OS were significantly decreased for the following pathological variables: increased cellularity (>300 nuclei per HPF), mitotic activity of >7 per 10 HPF, increased MIB-1 labeling index (LI), topoisomerase-IIalpha LI, S-phase fraction, and p53 and bcl-2 positivity. Increased cyclin D1 LI was demonstrated to have only a marginally significant impact on PFS. A flow chart modeling was further performed to formulate a scheme for discriminating of prognostic subgroups. Based on that, p53 immunopositivity and/or MIB-1 LI of >5% (after subtotal resection) or MIB-1 LI of >15% (after complete resection) were the strongest indicators of the tumor's aggressive behavior and of a poor prognosis of the disease. Foci of hypercellularity should be specifically looked for in ependymomas for assessing the immunohistochemical studies.


Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach.
Ewing sarcoma is a rare type of cancer that develops in the bones and soft tissues. Drug therapy represents an extensively used modality for the treatment of sarcomas. However, cancer cells tend to develop resistance to antineoplastic agents, thereby posing a major barrier in treatment effectiveness. Thus, there is a need to uncover the molecular mechanisms underlying chemoresistance in sarcomas and, hence, to enhance the anticancer treatment outcome. In this study, a differential gene expression analysis was conducted on high-throughput transcriptomic data of chemoresistant versus chemoresponsive Ewing sarcoma cells. By applying functional enrichment analysis and protein-protein interactions on the differentially expressed genes and their corresponding products, we uncovered genes with a hub role in drug resistance. Granted that non-coding RNA epigenetic regulators play a pivotal role in chemotherapy by targeting genes associated with drug response, we investigated the non-coding RNA molecules that potentially regulate the expression of the detected chemoresistance genes. Of particular importance, some chemoresistance-relevant genes were associated with the autonomic nervous system, suggesting the involvement of the latter in the drug response. The findings of this study could be taken into consideration in the clinical setting for the accurate assessment of drug response in sarcoma patients and the application of tailored therapeutic strategies.


Milk fat globule membrane supplementation with voluntary running exercise attenuates age-related motor dysfunction by suppressing neuromuscular junction abnormalities in mice.
Age-related loss of skeletal muscle mass and function attenuates physical performance, and maintaining fine muscle innervation is known to play an important role in its prevention. We had previously shown that consumption of milk fat globule membrane (MFGM) with habitual exercise improves the muscle mass and motor function in humans and mice. Improvement of neuromuscular junction (NMJ) was suggested as one of the mechanisms underlying these effects. In this study, we evaluated the effect of MFGM intake combined with voluntary running (MFGM-VR) on morphological changes of NMJ and motor function in aging mice. Seven months following the intervention, the MFGM-VR group showed a significantly improved motor coordination in the rotarod test and muscle force in the grip strength test compared with the control group at 13 and 14months of age, respectively. In 14-month old control mice, the extensor digitorum longus muscle showed increased abnormal NMJs, such as fragmentation and denervation, compared with 6-month old young mice. However, such age-related deteriorations of NMJs were significantly suppressed in the MFGM-VR group. Increase in the expression of NMJ formation-related genes, such as agrin and LDL Receptor Related Protein 4 (LRP4), might contribute to this beneficial effect. Rotarod performance and grip strength showed significant negative correlation with the status of denervation and fragmentation of NMJs. These results suggest that MFGM intake with voluntary running exercise effectively suppresses age-related morphological deterioration of NMJ, thus contributing to improvement of motor function.


Effects of Δ-THC on Working Memory: Implications for Schizophrenia?
This article reviews the literature on the acute effects of Delta 9-tetrahydrocannabinol, the primary psychoactive component of marijuana, on working memory, and the implications for schizophrenia. Working memory deficits are a hallmark feature of schizophrenia, and have been implicated as an etiologic mechanism contributing to the onset of the disorder. Regular marijuana smokers may also exhibit subtle working memory impairment relative to healthy controls, and an association between marijuana abuse and subsequent development of schizophrenia, though controversial, has been reported in the literature. The causal role that marijuana plays in working memory impairment related to schizophrenia, however, remains unclear. Thus, this article specifically considers the acute effects of marijuana on working memory performance. The ecologic relevance and clinical significance of these findings will be examined, and directions for future research will be recommended.


A localized surface protein of guinea pig sperm exhibits free diffusion in its domain.
Using the technique of fluorescence redistribution after photobleaching, we are studying the cellular mechanisms involved in localizing surface molecules to particular domains. A number of antigens localized to discrete surface regions have been identified with monoclonal antibodies on guinea pig sperm cells ( Primakoff , P., and D. G. Myles , 1983, Dev. Biol., 98:417-428). One of these monoclonal antibodies, PT-1, binds exclusively to the posterior tail region of the sperm cell surface. PT-1 recognizes an integral membrane protein that in complex with n-octyl-beta-D-glucopyranoside has a sedimentation coefficient of 6.8S in sucrose density gradients. Fluorescence redistribution after photobleaching measurements reveal that within its surface domain the PT-1 antigen diffuses rapidly (D = 2.5 X 10(-9) cm2/s) and completely (greater than 90% recovery after bleaching). These results rule out for this membrane protein all models that invoke immobilization as a mechanism for maintaining localization. We propose that the mechanism for localization of the PT-1 antigen may be a barrier to diffusion at the domain boundary.


Temporal Modulation of Stem Cell Activity Using Magnetoactive Hydrogels.
Cell activity is coordinated by dynamic interactions with the extracellular matrix, often through stimuli-mediated spatiotemporal stiffening and softening. Dynamic changes in mechanics occur in vivo through enzymatic or chemical means, processes which are challenging to reconstruct in cell culture materials. Here a magnetoactive hydrogel material formed by embedding magnetic particles in a hydrogel matrix is presented whereby elasticity can be modulated reversibly by attenuation of a magnetic field. Orders of magnitude change in elasticity using low magnetic fields are shown and reversibility of stiffening with simple permanent magnets is demonstrated. The broad applicability of this technique is demonstrated with two therapeutically relevant bioactivities in mesenchymal stem cells: secretion of proangiogenic molecules, and dynamic control of osteogenesis. The ability to reversibly stiffen cell culture materials across the full spectrum of soft tissue mechanics, using simple materials and commercially available permanent magnets, makes this approach viable for a broad range of laboratory environments.


Admission Clinicopathological Factors Associated with Prolonged Hospital Stay Among Hospitalized Patients with Dengue Viral Infections.
Background: There is an escalation of frequency and magnitude of dengue epidemics in Malaysia, with a concomitant increase in patient hospitalization. Prolonged hospitalization (PH) due to dengue virus (DENV) infections causes considerable socioeconomic burden. Early identification of patients needing PH could optimize resource consumption and reduce health care costs. This study aims to identify clinicopathological factors present on admission that are associated with PH among patients with DENV infections. Methods: This study was conducted in a tertiary referral hospital in Southern Malaysia. Relevant clinical and laboratory data upon admission were retrieved from medical records of 253 consecutive DENV nonstructural protein 1 (NS1) antigen and PCR-positive hospitalized patients. The DENV serotype present in each patient was determined. Patients were stratified based on duration of hospital stay (<4 vs. ≥4 days). Data were analyzed using IBM® SPSS® 25.0. Multivariate logistic regression was performed to examine the association between PH and admission parameters. Results: Of 253 DENV hospitalized patients, 95 (37.5%) had PH (≥4 days). The mean duration of hospital stay was 3.43 ± 2.085 days (median = 3 days, interquartile range = 7 days). Diabetes mellitus (adjusted odds ratio [AOR] = 6.261, 95% confidence interval [CI] = 2.130-18.406, p = 0.001), DENV-2 serotype (AOR = 2.581, 95% CI = 1.179-5.650, p = 0.018), duration of fever ≤4 days (AOR = 2.423, 95% CI = 0.872-6.734, p = 0.09), and a shorter preadmission fever duration (AOR = 0.679, 95% CI = 0.481-0.957, p = 0.027) were independently associated with PH. However, PH was not found to be associated with symptoms on admission, secondary DENV infections or platelet count, hematocrit, or liver enzyme levels on admission. Conclusions: Early identification of these factors at presentation may alert clinicians to anticipate and recognize challenges in treating such patients, leading to more focused management plans that may shorten the duration of hospitalization.


Histoplasmosis of the colon in patients with AIDS: imaging findings in four cases.
The purpose of this study was to describe and illustrate the radiographic findings of colonic histoplasmosis in patients with AIDS. Four HIV-positive patients were admitted because of fever, abdominal pain, tenderness, weight loss, and diarrhea. One patient had known disseminated histoplasmosis, one had esophageal moniliasis, and two had no other known opportunistic infections or tumors. All four patients had barium enemas, and two had abdominal CT examinations. The diagnosis was established via colonoscopic biopsy in three patients and with surgery in one patient. Barium enema in two patients showed separate, short, apple-core lesions in the transverse and descending colon. In one patient, a single lesion in the ascending colon mimicked colonic carcinoma. One patient had segmental involvement of the ascending colon, compatible with inflammatory bowel disease. CT examination revealed circumferential thickening of the wall of the colon with adjacent lymphadenopathy of mixed attenuation. Three patients responded to medical therapy, and one patient remained symptomatic and was found on a follow-up CT examination to have significant recurrence of retroperitoneal lymphadenopathy. Colonic histoplasmosis in patients with AIDS has protean radiographic features and can mimic colonic carcinoma. In these patients, histoplasmosis should be part of the differential diagnosis, particularly when several colonic lesions are detected, associated regional and retroperitoneal lymphadenopathy is present, and the patient is living or has lived in an endemic area.


Bereavement and the elderly: a critical review with implications for nursing practice and research.
Loss is a common occurrence in the lives of the elderly. One of the most profound losses is the death of a spouse. Yet, infrequent and predictable as this event is for older adults, we know very little about the grieving process or the resolution of grief among this age group. For nurses who care for older clients an understanding of loss and bereavement is important in order to provide appropriate and timely support. In this paper the nature of grief and bereavement behaviour is discussed beginning with the earliest empirical work done in 1930 and including a synopsis of six major variations of grief. A comprehensive review and critique of current investigations provides the basis for suggesting that, because of flaws in conceptualization and design, there are substantial limits on the relevance of existing knowledge of grief for an understanding of this phenomenon among the aged bereaved. A beginning theoretical integration and discussion of key concepts related to bereavement and the elderly is provided. This discussion is summarized in a proposed model. This paper concludes with suggestions for nursing research and practice.


[Histomorphology of inflammation].
Progress in biochemistry of inflammation, particularly in the identification of mediators of inflammation, has considerably deepened our understanding of the histomorphology of inflammatory lesions. In surgical pathology, the traditional histologic differentiation between specific and non-specific inflammation still plays a certain role. This differentiation, on the other hand, has lost significance since it became evident that specific inflammatory reactions, such as epithelioid cell granuloma formation, can be observed in diseases of completely different etiology. Consequently, the histological picture does not reflect the activity of a particular etiologic agent but rather images the action of mediators of inflammation. Which mediators are released depends not only on the inducing agent but also on numerous other factors. This holds true for specific as well as non-specific inflammation and also for immunopathologic (allergic) reactions. In most instances the modulating effect of the fine structure of tissues (e.g. capillary angioarchitecture) on the intensity, type and course of inflammatory processes is covered by other predominating influences. The most important new aspect in the histomorphology of inflammation is the possibility--nowadays--of interpreting histological patterns of inflammation in terms of known pathomechanisms.


Reduction of foveal sensitivity in diabetic macular edema with visual acuity 20/20.
To compare foveal sensitivity in eyes with and without diabetic macular edema, with 20/20 visual acuity. Non-experimental, comparative, prospective, cross sectional study in eyes with and without retinopathy and focal macular edema, with 20/20 visual acuity. The sample was divided in 3 groups: (1) non-diabetic subjects, (2) diabetics without retinopathy, and 3) diabetics with non-proliferative retinopathy and clinically significant macular edema. Median foveal sensitivity was compared between groups (Kruskal Wallis test). 86 eyes (28 in group 1, 26 in group 2 and 32 in group (3). Medians shown a statistical difference between groups (p = 0.001). Median foveal sensitivity was significantly lower in group 3 than in group 1 (p = 0.001) and than in group 2 (p = 0.03). Median foveal sensitivity did not differ between groups 1 and 2 (p = 0.10). Foveal sensitivity in diabetic macular edema and visual acuity 20/20 is lower in eyes with center sparing clinically significant macular edema and 20/20 visual acuity. The prognostic value of this dysfunction requires evaluation, in order to learn whether early treatment is required in these eyes.


A multicenter clinical study of cefoperazone.
Thirty-five adult and 11 pediatric patients in nine Philippine hospitals were treated with cefoperazone for various moderate to severe infections. Adults received 1 to 8 gm/day and children received 0.450 to 4 gm/day in two divided doses, for a mean period of eight to nine days (ranges, 5 to 11 days for children and 5 to 30 days for adults). The efficacy rate (cured and improved) was 90.90% for pediatric patients and 85.72% for adult patients. In a group of patients shifted from other antibiotic regimens, efficacy rates were 100% for pediatric patients and 85% for adult patients treated with cefoperazone. No follow-up cultures were obtained from patients from whom 26 pathogens were isolated, but correlations between the isolates and clinical efficacy showed that cefoperazone had an efficacy rate of 92.3%.


Strong evidence of association between obesity and some cancers.
A large review lead by researchers at Imperial College London has discovered 'strong evidence' to support the association between obesity and some major types of cancer, mainly those related to digestive organs and hormone-related malignancies.


Nanoleakage evaluation at adhesive-dentin interfaces by different observation methods.
The purpose of this study was to evaluate the capability and characteristics of different nanoleakage observation methods, including light microscope (LM), field-emission scanning electron microscope (FESEM), transmission electron microscope (TEM), and confocal laser scanning microscope (CLSM). Dentin specimens were bonded with either an etch-and-rinse adhesive (SBMP) or a self-etch adhesive (GB), and prepared for nanoleakge evaluation according to different observation methods. LM, FESEM and CLSM results demonstrated that the SBMP group showed more interfacial nanoleakage than the GB group (p<0.05); by contrast, no significant difference was found in TEM results (p>0.05), however, TEM illustrated concrete nanoleakage forms or patterns. The results suggested that different observation methods might exhibit distinct images and a certain degree of variations in nanoleakage statistical results. Researchers should carefully design and calculate the optimum assembly in combination with qualitative and quantitative approaches to obtain objective and accurate nanoleakage evaluation.


Prevalence and Predictors of Violence Against Women in Pakistan.
Violence against Pakistani women occurs at an alarming prevalence that reflects a significant risk to the health of women and families. Understanding violence against women in Pakistan comes with methodological and cultural complexities. Many of the studies examining prevalence and predictors of violence against women tend to utilize convenience samples contributing to the possibility of an inflated prevalence. Due to the patriarchal family structure and cultural context, domestic violence is normalized resulting in extremely low reporting rates. The present study utilizes a sample of ever-married Pakistani women collected across five provinces to shed light on the prevalence and predictors of women that experience domestic violence (emotional or physical abuse). Data were obtained from the 2012-2013 Pakistan Demographic and Health Survey including a large sample of Pakistani women from five provinces (Sindh, Punjab, Balochistan, Khyber Pakhtunkhwa, and Gilgit Baltistan). Binary Linear regressions were conducted to examine how intrinsic variables (age, education, region, urban/rural, type of marital relationship, and wealth) predicted experiencing emotional or physical abuse from one's husband within the past year. Approximately, 20% of women endorsed experiencing physical violence and 28% endorsed experiencing emotional violence. Results found that educational level, wealth, and type of marital relationship were associated with a higher likelihood of experiencing some form of physical or emotional violence. Implications from this study support policy interventions aimed at education within the family, linking women with resources, and continued investment in the education of young women. Interventions would be best targeted in low wealth regions with a special emphasis on rural areas.


Some properties of starches of grain amaranths and several millets.
Starch granules were prepared from seeds of Amaranthus hypochondriacus L., A. caudatus L., proso millet, Japanese barnyard millet and foxtail millet. Amylose contents and the distribution of alpha-1,4 linked chain of amylopectin were determined by gel filtration of isoamylase-debranched starches. Some physical and chemical properties of the starches were also examined by scanning electron microscopy, X-ray diffractometry, photopastegraphy, and differential scanning calorimetry, together with starch-granule susceptibility to amylases. The existence of both normal and waxy types in the same species of a grain amaranth, A. hypochondriacus L., was confirmed. A. caudatas starches were identified to consist of mainly typical amylopectin and 5-7% amylose. The starches have some unique properties, namely, high starch-granule susceptibility values to amylases as well as those of A. hypochondriacus and unique pasting properties.


EEG-fMRI correlation patterns in the presurgical evaluation of focal epilepsy: a comparison with electrocorticographic data and surgical outcome measures.
EEG-correlated functional MRI (EEG-fMRI) visualizes brain regions associated with interictal epileptiform discharges (IEDs). This technique images the epileptiform network, including multifocal, superficial and deeply situated cortical areas. To understand the role of EEG-fMRI in presurgical evaluation, its results should be validated relative to a gold standard. For that purpose, EEG-fMRI data were acquired for a heterogeneous group of surgical candidates (n=16) who were later implanted with subdural grids and strips (ECoG). The EEG-fMRI correlation patterns were systematically compared with brain areas involved in IEDs ECoG, using a semi-automatic analysis method, as well as to the seizure onset zone, resected area, and degree of seizure freedom. In each patient at least one of the EEG-fMRI areas was concordant with an interictally active ECoG area, always including the early onset area of IEDs in the ECoG data. This confirms that EEG-fMRI reflects a pattern of onset and propagation of epileptic activity. At group level, 76% of the BOLD regions that were covered with subdural grids, were concordant with interictally active ECoG electrodes. Due to limited spatial sampling, 51% of the BOLD regions were not covered with electrodes and could, therefore, not be validated. From an ECoG perspective it appeared that 29% of the interictally active ECoG regions were missed by EEG-fMRI and that 68% of the brain regions were correctly identified as inactive with EEG-fMRI. Furthermore, EEG-fMRI areas included the complete seizure onset zone in 83% and resected area in 93% of the data sets. No clear distinction was found between patients with a good or poor surgical outcome: in both patient groups, EEG-fMRI correlation patterns were found that were either focal or widespread. In conclusion, by comparison of EEG-fMRI with interictal invasive EEG over a relatively large patient population we were able to show that the EEG-fMRI correlation patterns are spatially accurate at the level of neurosurgical units (i.e. anatomical brain regions) and reflect the underlying network of IEDs. Therefore, we expect that EEG-fMRI can play an important role for the determination of the implantation strategy.


Capillary filling in microchannels patterned by posts.
We investigate the capillary filling of three-dimensional microchannels with surfaces patterned by posts of square cross section. We show that pinning on the edges of the posts suppresses and can halt capillary filling. We stress the importance of the channel walls in controlling whether filling can occur. In particular for channels higher than the distance between adjacent posts, filling occurs for contact angles less than a threshold angle of approximately 55 degrees , independent of the height of the channel.


A simple solid media assay for detection of synergy between bacteriophages and antibiotics.
The emergence of antibiotic resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. While phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation and purification have enabled a reevaluation of their utility in contemporary clinical medicine. In most phage therapy cases, phages are administered in combination with antibiotics to ensure that patients receive the standard-of-care treatment. Some phages may work cooperatively with antibiotics to eradicate ARB, as often determined using non-standardized broth assays. We sought to develop a solid media-based assay to assess cooperativity between antibiotics and phages to offer a standardized platform for such testing. We modeled the interactions that occur between antibiotics and phages on solid medium to measure additive, antagonistic, and synergistic interactions. We then tested the method using different bacterial isolates, and identified a number of isolates where synergistic interactions were identified. These interactions were not dependent on the specific organism, phage family, or antibiotic used. A priori susceptibility to the antibiotic or the specific phage were not requirements to observe synergistic interactions. Our data also confirm the potential for the restoration of vancomycin to treat Vancomycin Resistant Enterococcus (VRE) when used in combination with phages. Solid media assays for the detection of cooperative interactions between antibiotics and phages can be an accessible technique adopted by clinical laboratories to evaluate antibiotic and phage choices in phage therapy.


[Evaluation of the seroconversion as a response to rabies vaccination in dogs, Valle del Cauca, Colombia, 2009].
The province of Valle del Cauca has been free of dog rabies for more than 20 years. However, sylvatic rabies foci remain which are threats to the health of the populace and its pets. Rabies vaccination campaigns are carried out annually in all 42 counties of the province. The impact of dog vaccination was evaluated on the basis of humoral immunoresponse, population parameters and correlation with variables inherent to the vaccination process and logistics. Sera and associated data were obtained from each of the 42 counties for a total sample of 569 rabies-vaccinated dogs. Rabies neutralizing antibodies were measured by quantitative ELISA. The data were analyzed with the statistical programs in Epi-Info 6.0. Nearly 10% of dogs were seronegative (9.1%) and an additional 25.1% did not elicit an adequate humoral immune response to vaccination. Concentration of rabies neutralizing antibodies diminished gradually with the time after vaccination and was correlated with dog age and vaccine quality. No associations were noted between dog gender or breed. These data permit the following recommendations: (1) only viable, non expired rabies vaccines must be used to immunize animals, (2) two doses of rabies vaccine must be applied during the first six months of dog life, (3) booster immunizations must be administered every year, (4) practices and processes related to rabies vaccination in private institutions must inspected regularly by health authorities.


Daily rhythms of diabetogenic factors in men: role of type 2 diabetes and body weight.
Obesity is a major cause of type 2 diabetes. Transition from obesity to type 2 diabetes manifests in the dysregulation of hormones controlling glucose homeostasis and inflammation. As metabolism is a dynamic process that changes across 24 h, we assessed diurnal rhythmicity in a panel of 10 diabetes-related hormones. Plasma hormones were analysed every 2 h over 24 h in a controlled laboratory study with hourly isocaloric drinks during wake. To separate effects of body mass from type 2 diabetes, we recruited three groups of middle-aged men: an overweight (OW) group with type 2 diabetes and two control groups (lean and OW). Average daily concentrations of glucose, triacylglycerol and all the hormones except visfatin were significantly higher in the OW group compared to the lean group (P < 0.001). In type 2 diabetes, glucose, insulin, C-peptide, glucose-dependent insulinotropic peptide and glucagon-like peptide-1 increased further (P < 0.05), whereas triacylglycerol, ghrelin and plasminogen activator inhibitor-1 concentrations were significantly lower compared to the OW group (P < 0.001). Insulin, C-peptide, glucose-dependent insulinotropic peptide and leptin exhibited significant diurnal rhythms in all study groups (P < 0.05). Other hormones were only rhythmic in 1 or 2 groups. In every group, hormones associated with glucose regulation (insulin, C-peptide, glucose-dependent insulinotropic peptide, ghrelin and plasminogen activator inhibitor-1), triacylglycerol and glucose peaked in the afternoon, whereas glucagon and hormones associated with appetite and inflammation peaked at night. Thus being OW with or without type 2 diabetes significantly affected hormone concentrations but did not affect the timing of the hormonal rhythms.


Man-made maladies and medicine.
Man-made, including iatrogenic, maladies are usually unforeseen and may fall into several categories: those resulting from diagnosis and treatment, those relating to social and psychological attitudes or situations, and those emanating from mass programs to control or eradicate diseases. the physician-originated spread of "shipyard eye," tactless behavior toward patients, and lapses in malaria eradication programs. From a presentation of some results from acts of good intention, we may come to anticipate at least some of the unanticipated consequences of health-related interference, much as we are all becoming aware of other consequences of man's tampering with earthly resources.


Synergism of 64Cu-Labeled RGD with Anti-PD-L1 Immunotherapy for the Long-Acting Antitumor Effect.
We put forward a novel targeting-triggering-therapy (TTT) scheme that combines 64Cu-based targeted radionuclide therapy (TRT) with programmed death-ligand 1 (PD-L1)-based immunotherapy for enhancing therapeutic efficacy. The αvβ3 integrin-targeted 64Cu-DOTA-EB-cRGDfK (64Cu-DER) was synthesized. Flow cytometry, immunofluorescence staining, and RT-qPCR were performed to verify PD-L1 upregulation after irradiation with 64Cu-DER. Positron emission tomography imaging was performed to investigate the prominent tumor retention property of 64Cu-DER. In the MC38 tumor model, anti-PD-L1 antibody (αPD-L1 mAb) was delivered in a concurrent or sequential manner after 64Cu-DER was injected, followed by the testing of changes in tumor microenvironment (TME). PD-L1 was upregulated in a time- and dose-dependent manner after being induced by 64Cu-DER. The combination of 64Cu-DER TRT (925 MBq/kg) and αPD-L1 mAb (10 mg/kg) resulted in significant delay in tumor growth and protected against tumor rechallenge. Blockade of PD-L1 at 4 h after 64Cu-DER TRT (64Cu-DER + αPD-L1 mAb @ 4 h combination group) was able to achieve 100% survival rate, prevent tumor relapse, and evidently prolong the survival of mice. In summary, the combination of 64Cu-DER and αPD-L1 mAb in a time-dependent manner could be a promising approach to improve therapeutic efficacy. Understandably, this strategy has the potential to extend the scope of 64Cu-based TTT and merits translation into clinical practice for the better management of immune checkpoint blockade immunotherapy.


[Prediction of Prognosis in Breast Carcinoma Using Klotho Immunohistochemistry].
Klotho is one of the known anti-aging genes, and functions as an inhibitor of the insulin-like growth factor 1(IGF-1) pathway. However, the clinical significance of Klotho expression in cancer tissues have not been elucidated yet. In this study, we aimed to investigate the clinical significance of Klotho expression in breast cancer patients. We evaluated Klotho expression through immunohistochemical analysis and evaluating Ki-67 positive cell index in 142 patients who underwent surgery for breast cancer in our hospital. There was no significant correlation between age, menopausal state, historical type, hormone status, HER2 status, and distant metastases. High expression of Klotho was observed in the non-invasive compared to the invasive ductal carcinomas. The number of metastatic lymph nodes, clinical stage, and tumor size were correlated to Klotho expression level in the cancer tissues. The Klotho positive group exhibited low score for Ki-67 positive cell index than the Klotho negative group. No significant correlation in cumulative survival rates between Klotho positive and Klotho negative groups was observed. The Klotho negative group exhibited good prognosis than the Klotho positive group for the disease- free survival after the operation. These results suggest that the analysis Klotho expression in the breast cancer tissues using immunohistochemistry is a useful tool to assess the disease-free survival for breast cancer patients.


Intracellular localization of carbonic anhydrase in some vertebrate nephrons.
The Hansson histochemical method for carbonic anhydrase has been modified by embedding of the tissue in a resin before sectioning and incubation. While retaining the now generally accepted validity and specificity of the original method it has several advantages. It is simple and rapid and appears to give unusually sharp localization of the stain. The section thickness may be varied to suit light microscopy and electron microscopy with resolution down to 25 A. The method has been discussed especially with regard to false localization. The intracellular distribution of carbonic anhydrase in the kidneys of frogs, rats and birds has been examined. As a basis for the histochemical investigation an ultrastructural analysis of the avian nephron has been performed, using mainly young swifts. Thin tubules are found exclusively in medullary nephrons, and their cells are of an unusual structure combining high cell thickness with strong development of the paracellular route. The avian initial collecting tubule contains a high proportion of dark cells containing mainly baso-lateral carbonic anhydrase. The distribution and morphology of dark cells in vertebrate nephrons has been surveyed. These cells are also compared with oxyntic cells and it is suggested that the cells are responsible for the terminal acidification of urine taking place in the kidney. A simplified terminology for the vertebrate nephron is suggested.


Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN.
The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.


Overexpression of X-linked inhibitor of apoptosis in human hepatocellular carcinoma.
The X-linked inhibitor of apoptosis (XIAP) is a member of a novel family of inhibitors of apoptosis. Since suppression of apoptosis is fundamentally important for carcinogenesis and tumor growth, we investigated the expression and function of XIAP in human hepatocellular carcinomas (HCCs). XIAP was expressed constitutively in HCC cell lines. Fourteen out of 20 (70%) HCC tissues demonstrated moderate or strong cytoplasmic staining for XIAP, whereas non-tumor parts showed negative or weak staining for XIAP by immunohistochemistry. In addition, XIAP expression was inversely correlated with apoptosis, but not with proliferation in HCC tissues. These results indicated that XIAP is a principal inhibitor of apoptosis overexpressed in human HCCs and that XIAP may be a potential target for gene therapy of human HCCs.


Direct generation of starting points for freeform off-axis three-mirror imaging system design using neural network based deep-learning.
In this paper, we propose a framework of starting points generation for freeform reflective triplet using back-propagation neural network based deep-learning. The network is trained using various system specifications and the corresponding surface data obtained by system evolution as the data set. Good starting points of specific system specifications for further optimization can be generated immediately using the obtained network in general. The feasibility of this design process is validated by designing the Wetherell-configuration freeform off-axis reflective triplet. The amount of time and human effort as well as the dependence on advanced design skills are significantly reduced. These results highlight the powerful ability of deep learning in the field of freeform imaging optical design.


Orthostatic hypotension in spinal cord injured patients.
Treatment of orthostatic hypotension is an important consideration for many patients with spinal cord injuries, especially those with an injury to the cervical cord. Delay in attainment of an upright sitting posture can cause a delay in the completion of rehabilitation. Although most trials of medications used in the treatment of orthostatic hypotension have been performed on non-spinal cord injured patients, this paper provides a review of both pharmacological and non-pharmacologic means of therapy. Normally, regulation of mean arterial pressure occurs through several different mechanisms; long-term control is via the renal system and short-term control is via the nervous system. These mechanisms will be discussed, as well as causes of orthostatic hypotension in spinal cord injured patients, and the normalization of blood pressure control which generally occurs to some degree following a spinal cord injury.


miR-127 enhances myogenic cell differentiation by targeting S1PR3.
MicroRNAs (miRNAs) have recently been implicated in muscle stem cell function. miR-127 is known to be predominantly expressed in skeletal muscle, but its roles in myogenic differentiation and muscle regeneration are unknown. Here, we show that miR-127 is upregulated during C2C12 and satellite cell (SC) differentiation and, by establishing C2C12 cells stably expressing miR-127, demonstrate that overexpression of miR-127 in C2C12 cells enhances myogenic cell differentiation. To investigate the function of miR-127 during muscle development and regeneration in vivo, we generated miR-127 transgenic mice. These mice exhibited remarkably accelerated muscle regeneration compared with wild-type mice by promoting SC differentiation. Mechanistically, we demonstrated that the gene encoding sphingosine-1-phosphate receptor 3 (S1PR3), a G-protein-coupled receptor for sphingosine-1-phosphate, is a target of miR-127 required for its function in promoting myogenic cell differentiation. Importantly, overexpression of miR-127 in muscular dystrophy model mdx mice considerably ameliorated the disease phenotype. Thus, our findings suggest that miR-127 may serve as a potential therapeutic target for the treatment of skeletal muscle disease in humans.


Interaction of bilingualism and Attention-Deficit/Hyperactivity Disorder in young adults.
One hundred and sixty-eight young adult participants were classified as monolingual or bilingual and as having a previously reported clinical diagnosis of ADHD or not to create four groups. All participants completed tests of language proficiency, ADHD ratings, and executive control. Both bilingualism and ADHD are generally associated with poorer vocabulary knowledge, but bilingualism and ADHD are associated with opposite effects on executive control. Consistent with this literature, bilinguals performed more poorly than monolinguals on the vocabulary test but contrary to predictions, the ADHD group performed somewhat better on language ability than the non-ADHD group, attesting to their high functioning status. For the flanker task, both bilinguals and non-ADHD participants showed less cost in performing in the conflict condition than in the baseline condition. For the stop-signal task, ADHD status interfered more with performance by bilinguals than monolinguals, suggesting a greater burden of ADHD on executive function for this group.


Protective effect of garlic extract against maternal and foetal cerebellar damage induced by lead administration during pregnancy in rats.
In spite of its industrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilisation of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic. In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and foetal cerebellar damage produced by administration of different doses of Pb during pregnancy. Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.w. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/kg b.w./day of garlic extract). Treatments started from day 1 to day 20 of pregnancy, where the mother rats of different experimental groups were sacrificed to obtain the foetuses. Pb level in the maternal and foetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and foetal groups were processed to histological and immunohistochemical staining for microscopic examination. The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and foetuses in the form of decrease in maternal weight gain, placental and foetal weights, brain weight and diminished foetal growth parameters, which were prominent in rat's group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared with the control group. The histopathological examination of the cerebellum of treated dams and foetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of development of foetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes. This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of foetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and foetuses. (Folia Morphol 2018; 77, 1: 1-15).


Sorbent Mass Variation Method: A New Possibility for the Determination of Binding Isotherms.
Measurement of equilibrium mass fraction of a surfactant as a function of the sorbent mass fraction was performed on gel sorbent-solution systems in order to determine binding isotherms and to calculate fundamental characteristics of the solvation layer. With application of this new method, it was possible to calculate specific solvation/sorption capacity and absolute average local composition of the solvation layer. It has been pointed out by systematic variation of the composition (hydrophobicity) and degree of cross-linking of the gel sorbents that the ratio of components in the solvation layer can be constant in a given range of equilibrium mass fraction of the sodium dodecyl sulfate (SDS) and that the specific solvation/sorption capacity of gel sorbents can be much greater than that of activated carbon type adsorbents. On the basis of a mixed sorbent model, it turned out from calculations that there is no preferential binding of SDS close to the chemical cross-links and that the surfactant molecules prefer vinyl acetate groups as binding sites. The density of cross-links regulates the aggregation number of the bound surfactant as well. For loose gels, both binding isotherms and swelling curves show that the surfactant-polymer interaction is a strongly cooperative process. The result of these experiments may influence the general concept of solvation/sorption isotherms and all related phenomena.


Dewetting-Assisted Patterning: A Lithography-Free Route to Synthesize Black and Colored Silicon.
We report the use of thermal dewetting to structure gold-based catalytic etching masks for metal-assisted chemical etching (MACE). The approach involves low-temperature dewetting of metal films to generate metal holey meshes with tunable morphologies. Combined with MACE, dewetting-assisted patterning is a simple, benchtop route to synthesize Si nanotubes, Si nanowalls, and Si nanowires with defined dimensions and optical properties. The approach is compatible with the synthesis of both black and colored nanostructured silicon substrates. In particular, we report the lithography-free fabrication of silicon nanowires with diameters down to 40 nm that support leaky wave-guiding modes, giving rise to vibrant colors. Additionally, micrometer-sized areas with tunable film composition and thickness were patterned via shadow masking. After dewetting and MACE, such patterned metal films produced regions with distinct nanostructured silicon morphologies and colors. To-date, the fabrication of colored silicon has relied on complicated nanoscale patterning processes. Dewetting-assisted patterning provides a simpler alternative that eliminates this requirement. Finally, the simple transfer of resonant SiNWs into ethanolic solutions with well-defined light absorption properties is reported. Such solution-dispersible SiNWs could open new avenues for the fabrication of ultrathin optoelectronic devices with enhanced and tunable light absorption.


Structural changes in surface and bulk LiNi0.5Mn0.5O2 during electrochemical reaction on epitaxial thin-film electrodes characterized by in situ X-ray scattering.
Surface and bulk structural changes of LiNi(0.5)Mn(0.5)O(2) were investigated during electrochemical reaction using synchrotron X-ray scattering and a restricted reaction plane consisting of two-dimensional epitaxial-film electrodes. The changes in bulk structure confirmed lithium diffusion through the (110) surface, which was perpendicular to the two-dimensional (2D) edges of the layered structure. No (de)intercalation reaction was observed through the (003) surface at voltages of 3.0-5.0 V. However, intercalation did proceed through the (003) plane below 3.0 V, indicating unusual three-dimensional (3D) lithium diffusion in the over-lithiated 2D structure. During the electrochemical process, the surface of the electrode showed different structure changes from those of the bulk structure. The reaction mechanism of the intercalation electrodes for lithium batteries is discussed on the basis of surface and bulk structural changes.


The influence of market exclusivity on drug availability and medical innovations.
The interpretation and application of intellectual property laws is enormously complex in the pharmaceutical industry, with companies needing to obtain multiple patents to fully protect their innovations. While patents provide important incentives for biomedical innovation and economic growth, concern has been expressed over the growing number of patents, the granting of patents on basic research tools (eg, genetically engineered animals), and the possibility that these legal protections may ultimately inhibit scientific advancement.


Evaluation of the hyplex TBC PCR test for detection of Mycobacterium tuberculosis complex in clinical samples.
Tuberculosis (TB) is one of the major public health concerns worldwide. The detection of the pathogen Mycobacterium tuberculosis complex (MTBC) as early as possible has a great impact on the effective control of the spread of the disease. In our study, we evaluated the hyplex TBC PCR test (BAG Health Care GmbH), a novel assay using a nucleic acid amplification technique (NAAT) with reverse hybridisation and ELISA read out for the rapid detection of M. tuberculosis directly in clinical samples. A total of 581 respiratory and non-respiratory specimens from our pneumological hospital and the National TB Institute of Uzbekistan were used for the evaluation of the PCR assay. Of these, 292 were classified as TB samples and 289 as non-TB samples based on the results of the TB cultures as reference method. The PCR results were initially used to optimise the cut-off value of the hyplex TBC test system by means of a ROC analysis. The overall sensitivity of the assay was determined to be 83.1%. In smear-positive TB samples, the sensitivity of the hyplex TBC PCR test was estimated to 93.4% versus 45.1% in smear-negative samples. The specificity of the test was 99.25%. Of the two specimens (0.75%) with false-positive PCR results, one yielded a culture positive for non-tuberculous mycobacteria. Based on the assumption of a prevalence of 8% TB positives among the samples in our diagnostic TB laboratory, the positive and negative predictive values were estimated to 90.4% and 98.5%, respectively. The hyplex TBC PCR test is an accurate NAAT assay for a rapid and reliable detection of M. tuberculosis in various respiratory and non-respiratory specimens. Compared to many other conventional NAAT assays, the hyplex TBC PCR test is in a low price segment which makes it an attractive option for developing and emerging countries with high TB burdens.


Comparison of Twitch Responses During Current- or Voltage-Controlled Transcutaneous Neuromuscular Electrical Stimulation.
Neuromuscular electrical stimulation (NMES) is an established method for functional restoration of muscle function, rehabilitation, and diagnostics. In this work, NMES was applied with surface electrodes placed on the anterior thigh to identify the main differences between current-controlled (CC) and voltage-controlled (VC) modes. Measurements of the evoked knee extension force and the myoelectric signal of quadriceps and hamstrings were taken during stimulation with different amplitudes, pulse widths, and stimulation techniques. The stimulation pulses were rectangular and symmetric biphasic for both stimulation modes. The electrode-tissue impedance influences the differences between CC and VC stimulation. The main difference is that for CC stimulation, variation of pulse width and amplitude influences the amount of nerve depolarization, whereas VC stimulation is only dependent on amplitude variations for pulse widths longer than 150 μs. An important remark is that these findings are strongly dependent on the characteristics of the electrode-skin interface. In our case, we used large stimulation electrodes placed on the anterior thigh, which cause higher capacitive effects. The controllability, voltage compliance, and charge characteristics of each stimulation technique should be considered during the stimulators design. For applications that require the activation of a large amount of nerve fibers, VC is a more suitable option. In contrast, if the application requires a high controllability, then CC should be chosen prior to VC.


Environmental Complexity and Reduced Stocking Density Promote Positive Behavioral Outcomes in Broiler Chickens.
The objective was to evaluate the impacts of a complex environment and stocking density on Ross 708 broiler chicken behaviors. Eight pens contained either high complexity (HC) or low complexity (LC) environments, and high (HD) or low (LD) density. Through focal-animal sampling, the frequency and duration of behaviors were recorded continuously for 5 min at two timepoints for one day in weeks 2, 4, and 7. Birds were active for 30% of the observed time, with birds showing more activity in HC compared with LC. Birds in HC pens spent more time preening and foraging than birds in LC pens, which was interpreted as a positive outcome. Dustbathing and play were not impacted by complexity, possibly due to the observation method. Birds were more frequently active at HD compared with LD, but did not spend more time being active, suggesting disturbances. Birds foraged, drank, and ate less frequently in HD compared with LD, presumably because birds had more difficulty accessing resources. Activity and active behaviors reduced as birds aged, while preening frequency increased, possibly due to frustration, but this was not confirmed. Perching was unaffected by age, showing a persistent motivation to perform the behavior. Our results indicate that a complex environment provides positive stimulation for foraging, locomotion, preening, and overall activity. Despite reduced activity, many benefits of the tested environmental complexity and low density persisted as birds aged.


Early hybrid approach and enteral feeding algorithm could reduce the incidence of necrotising enterocolitis in neonates with ductus-dependent systemic circulation.
The reported incidence of necrotising enterocolitis in neonates with complex CHD with ductus-dependent systemic circulation ranges from 6.8 to 13% despite surgical treatment; the overall mortality is between 25 and 97%. The incidence of gastrointestinal complications after hybrid palliation for neonates with ductus-dependent systemic circulation still has to be defined, but seems comparable with that following the Norwood procedure. We reviewed the incidence of gastrointestinal complications in a series of 42 consecutive neonates with ductus-dependent systemic circulation, who received early hybrid palliation associated with a standardised feeding protocol. The median age and birth weight at the time of surgery were 3 days (with a range from 1 to 10 days) and 3.07 kg (with a range from 1.5 to 4.5 kg), respectively. The median ICU length of stay was 7 days (1-70 days), and the median hospital length of stay was 16 days (6-70 days). The median duration of mechanical ventilation was 3 days. Hospital mortality was 16% (7/42). In the postoperative period, 26% of patients were subjected to early extubation, and all of them received treatment with systemic vasodilatory agents. Feeding was started 6 hours after extubation according to a dedicated feeding protocol. After treatment, none of our patients experienced any grade of necrotising enterocolitis or major gastrointestinal adverse events. Our experience indicates that the combination of an "early hybrid approach", systemic vasodilator therapy, and dedicated feeding protocol adherence could reduce the incidence of gastrointestinal complications in this group of neonates. Fast weaning from ventilatory support, which represents a part of our treatment strategy, could be associated with low incidence of necrotising enterocolitis.


Line-field confocal optical coherence tomography for the in vivo real-time diagnosis of different stages of keratinocyte skin cancer: a preliminary study.
The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non-invasive diagnostic techniques can support the diagnosis in real time, avoiding unnecessary biopsies. This study aimed to preliminarily define main imaging criteria and histological correlations of actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) using the novel device line-field confocal optical coherence tomography (LC-OCT). Dermoscopy and LC-OCT images of 73 histopathologically confirmed lesions (46 AKs, 11 BD and 16 SCCs) were included in the study. Exemplary lesions (10 AKs, 5 BD and 5 SCCs) were additionally investigated with optical coherence tomography and reflectance confocal microscopy. Most common LC-OCT findings of KC in the descriptive statistics were hyperkeratosis/parakeratosis, disruption of stratum corneum, broadened epidermis, basal and suprabasal keratinocyte atypia, dilated vessels/neoangiogenesis and elastosis/collagen alterations. In the univariate multinomial logistic regression, a preserved DEJ was less common in SCC compared with AK and BD, BD displayed marked keratinocyte atypia involving all epidermal layers (bowenoid pattern), while SCC showed ulceration, increased epidermal thickness, keratin plugs, acantholysis, not visible/interrupted DEJ and epidermal bright particles. LC-OCT increased the diagnostic confidence by 24.7% compared with dermoscopy alone. Our study describes for the first time specific LC-OCT features of different stages of KC and their histopathological correlates, focusing on keratinocyte morphology and architecture of the epidermis and DEJ. LC-OCT may open new scenarios in the bedside diagnosis, treatment planning and follow-up of KC.


Adenosine myocardial SPECT--its efficacy and safety and correlation with coronary angiogram.
The aim of this study was to determine the safety and efficacy of adenosine Tc99m sestamibi myocardial perfusion study under controlled conditions and to correlate the adenosine Tc99m sestamibi perfusion defects and the coronary angiography in patients investigated for coronary artery disease. This prospective study included 122 consecutive patients who underwent adenosine Tc99m sestamibi single photon emission computed tomography (SPECT) myocardial perfusion study. Seventy two patients had coronary angiographic correlation. All the patients who were referred by the cardiologists for stress myocardial perfusion scan who could not be stressed physiologically for one reason or the other were included in the study. Among the coronary angiography group the overall sensitivity, specificity, positive predictive value and negative predictive value of adenosine Tc99m sestamibi single photon emission computed tomography myocardial perfusion study for detecting significant coronary obstruction (diameter > or = 50%) were 94.4%, 79%, 85% and 92% respectively. The side effects were transient and required no treatment. We conclude adenosine Tc99m sestamibi single photon emission computed tomogram myocardial perfusion study is a reliable test with high sensitivity and specificity for the detection of coronary artery disease.


Isolated Pericardial Hydatid Cyst: A Case Report.
Cardiac echinococcosis is extremely rare, and cysts are found mostly within the myocardium. Most cardiac hydatid cysts are located in the left ventricular wall. Only a few cases of isolated pericardial hydatid cysts have been reported. Echocardiography, computed tomography and magnetic resonance imaging are important diagnostic tools for the diagnosis of echinococcosis. Herein, we report a rare case of isolated pericardial hydatid cyst who presented to our emergency department with complaints of mid-sternal chest pain and shortness of breath.


Trends in long head biceps tenodesis.
Tenodesis of the long head of the biceps tendon has become a popular surgical treatment option for patients with pain or instability attributed to a diseased or unstable biceps tendon. No previous studies have characterized the practice patterns of surgeons performing biceps tenodesis in the United States. To investigate current trends in both arthroscopic and open biceps tenodesis across time, sex, age, and region of the United States as well as associated charges. Descriptive epidemiology study. Patients who underwent biceps tenodesis (Current Procedural Terminology [CPT] codes 23430 and 29828) for the years 2008 through 2011 were identified using the PearlDiver Patient Record Database, including both private-payer and Medicare data. These cohorts were then assessed for associated diagnoses using International Classification of Diseases, 9th Revision, codes and concomitant procedures using CPT codes. These searches yielded procedural volumes, sex and age distribution, regional volumes, and average per-patient charges. A χ(2) linear-by-linear association analysis, Student t test, and linear regression were used for comparisons, with P < .05 considered significant. A total of 44,932 biceps tenodesis procedures were identified from 2008-2011. The incidence of biceps tenodesis procedures per 100,000 database patients increased 1.7-fold over the study period, from 8178 in 2008 to 14,014 in 2011 (P < .0001). An increase in the overall percentage volume was noted in patients aged 60-69 years (P = .039) and 20-29 years (P = .016). The overall charges for arthroscopic tenodesis increased at a rate significantly greater than that of open tenodesis (P < .0001). Rotator cuff tear or sprain, bicipital tenosynovitis, biceps tendon rupture, superior labral lesion, and osteoarthritis were the most common diagnoses associated with biceps tenodesis procedures. A significant increase in isolated biceps tenodesis was also observed over the study period, from 1967 patients in 2008 to 3565 patients in 2011, representing a 1.8-fold increase. The incidence of biceps tenodesis has increased yearly from 2008-2011. Arthroscopic tenodesis has emerged as a more popular technique. Charges associated with the procedure have increased significantly. Significant regional variations in procedural incidences exist.


Digest: No conflict of interest between the sexes for optimal immune response in threespine stickleback.
Will sex-specificparasite exposure lead to sexually antagonistic immune trait fitness optima? Despite female stickleback encountering parasites at a higher rate, De Lisle and Bolnick found no evidence of sexual conflict related to their primary immune trait. Both male and female fish suffered high costs of infection and immune response on reproduction. If costs of both immunity and infection are high and concordant, the sexual conflict will not arise despite different parasite exposure rates.


Subcellular innervation patterns of the calcitonin gene-related peptidergic efferent terminals in the chinchilla vestibular periphery.
We examined the ultrastructural distribution of calcitonin gene-related peptide immunoreactivity in the peripheral vestibular system of the chinchilla to study the innervation patterns of this efferent neuropeptide. Immunoelectron microscopic localization of calcitonin gene-related peptide immunoreactive terminals in the maculae and cristae revealed an extensive innervation pattern on the afferent vestibular pathway. Calcitonin gene-related peptide immuno-reactive terminals made synaptic contacts with the unmyelinated portions of the primary afferent vestibular dendrites innervating both type I and type II hair cells. Abundant synaptic contact between calcitonin gene-related peptide immunoreactive terminals and the chalices surrounding type I hair cells was observed. Direct contact between calcitonin gene-related peptide immunoreactive terminals and type II hair cells was observed. In addition, vesiculated efferent terminals without calcitonin gene-related peptide immunoreactivity were seen synapsing on the chalices of type II hair cells and on the surrounding type I hair cells. The primary afferent somata in the vestibular ganglion of Scarpa did not contain calcitonin gene-related peptide immunoreactivity. Unmyelinated calcitonin gene-related peptide immunoreactive axons passed among the primary afferent fibers in Scarpa's ganglion, and these fibers continued through the subepithelial regions of the vestibular end-organs. The calcitonin gene-related peptide immunoreactive axons ramified to produce numerous calcitonin gene-related peptide immunoreactive terminals throughout the neurosensory epithelium of the maculae and cristae. These data suggest that calcitonin gene-related peptide-mediated modulation of the afferent vestibular system is functionally important.


Clinical and immunological characteristics of 56 patients with systemic lupus erythematosus in Uganda.
The prevalence and burden of SLE in Africa are poorly understood. This health-facility-based retrospective study aimed to describe the frequency and the clinical and immunological characteristics of SLE in Uganda. We reviewed clinical notes of patients presenting with rheumatological complaints in two large rheumatology outpatient clinics in Uganda between January 2014 and December 2019. Of the 1019 charts reviewed, 5.5% (56) of the patients had confirmed SLE, with a median age of 29 (range: 14-65) years. The male-to-female ratio was ∼1:10, and 19.6% (11/56) of the patients had SLE and RA overlap syndrome. Patients presented with joint pains or swellings (n = 39, 69.6%), typical photosensitive malar rash (n = 34, 60.7%), oral ulceration (n = 23, 41.1%), anaemia (n = 14, 25.0%), hair loss and polyserositis (n = 12, 21.4% each), constitutional symptoms (n = 10, 17.9%), RP (n = 4, 7.1%) or LN (n = 3, 5.4%). ANA and anti-dsDNA autoantibodies were both positive in 25 (75.8%) of the 33 patients with available results. ANA titres were ≥1:160, with a median titre of 1:160 (range: 1:160 to 1:3200). Six patients had titres ≥1:320. The median dsDNA level was 80 (range: 40-283) IU. Ten patients had results of C3 and C4 complement protein levels and, of these, 4 patients had low C3 levels and 3 had low C4 levels. SLE is uncommon among patients presenting with rheumatological complains in Uganda. SLE overlaps with RA in our setting, and a majority of patients present to care with complications.


Carotenoid Distribution in Nature.
Carotenoids are naturally occurring red, orange and yellow pigments that are synthesized by plants and some microorganisms and fulfill many important physiological functions. This chapter describes the distribution of carotenoid in microorganisms, including bacteria, archaea, microalgae, filamentous fungi and yeasts. We will also focus on their functional aspects and applications, such as their nutritional value, their benefits for human and animal health and their potential protection against free radicals. The central metabolic pathway leading to the synthesis of carotenoids is described as the three following principal steps: (i) the synthesis of isopentenyl pyrophosphate and the formation of dimethylallyl pyrophosphate, (ii) the synthesis of geranylgeranyl pyrophosphate and (iii) the synthesis of carotenoids per se, highlighting the differences that have been found in several carotenogenic organisms and providing an evolutionary perspective. Finally, as an example, the synthesis of the xanthophyll astaxanthin is discussed.


Temporal patterns and geographic heterogeneity of Zika virus (ZIKV) outbreaks in French Polynesia and Central America.
Zika virus (ZIKV) transmission has been reported in 67 countries/territories in the Oceania region and the Americas since 2015, prompting the World Health Organization (WHO) to declare ZIKV as a Public Health Emergency of International Concern in February 2016, due to its strong association with medical complications such as microcephaly and Guillain-Barré Syndrome (GBS). However, a substantial gap in knowledge still exists regarding differing temporal pattern and potential of transmission of ZIKV in different regions of the world. We use a phenomenological model to ascertain the temporal patterns and transmission potential of ZIKV in various countries/territories, by fitting the model to Zika case data from Yap Island and French Polynesia in the Oceania region and 11 countries/territories with confirmed case data, namely, Colombia, Ecuador, French Guiana, Guadeloupe, Guatemala, Mexico, Nicaragua, Panama, Puerto Rico, Saint Martin, and Suriname, to pinpoint the waves of infections in each country/territory and to estimate the respective basic reproduction number R0. Six of these time series datasets resulted in statistically significant model fit of at least one wave of reported cases, namely that of French Polynesia, Colombia, Puerto Rico, Guatemala, Suriname and Saint Martin. However, only Colombia and Guatemala exhibited two waves of cases while the others had only one wave. Temporal patterns of the second wave in Colombia and the single wave in Suriname are very similar, with the respective turning points separated by merely a week. Moreover, the mean estimates of R0 for Colombia, Guatemala and Suriname, all land-based populations, range between 1.05 and 1.75, while the corresponding mean estimates for R0 of island populations in French Polynesia, Puerto Rico and Saint Martin are significantly lower with a range of 5.70-6.89. We also fit the Richards model to Zika case data from six main archipelagos in French Polynesia, suggesting the outbreak in all six island populations occurred during the same time, albeit with different peak time, with mean R0 range of 3.09-5.05. Using the same modeling methodology, in this study we found a significant difference between transmissibility (as quantified by R0) in island populations as opposed to land-based countries/territories, possibly suggesting an important role of geographic heterogeneity in the spread of vector-borne diseases and its future course, which requires further monitoring. Our result has potential implications for planning respective intervention and control policies targeted for island and land-based populations.


Lead exposure biomarkers in the Common Loon.
Lead in fishing tackle is a significant source of exposure to the environment, wildlife, and potentially humans. Common Loons (Gavia immer) are exposed to lead by eating fish which have lead tackle, or ingesting fishing weights or spent ammunition when they ingest small stones to aid in digestion. Blood lead is traditionally used as a biomarker of exposure in loons, but it only reflects recent exposures. Cumulative exposure measured via bone lead may better reflect the overall health of loons and their aquatic habitat. This study compared a portable x-ray fluorescence (XRF) device for measurement of bone lead with and without tissue overlying the bone on loon cadavers with measurements made by inductively coupled plasma mass spectrometry (ICP-MS) of different tissues from the loons. For this study we had 75 bone samples, 19 body fluid samples, and 17 liver lead samples. We found significant correlations between portable XRF bone lead measurements made with overlying tissue and ICP-MS measures of bone lead (R = 0.88), body fluid lead (R = 0.65), and liver lead (R = 0.71). Bone lead was found to be higher in loons collected from non-coastal regions. In assessing lead-related cause of death, bone lead proved more predictive than liver lead. Future studies should investigate the value of these biomarkers for both aquatic health and loon health to further validate our findings.


Dirhodium(II)-Catalyzed C(sp2 )-H Azidation of Benzaldehydes.
Invited for the cover of this issue is the group of Yuanhua Wang at Sichuan University. The image depicts the reported dirhodium complexes depicted as Chinese lanterns. Read the full text of the article at 10.1002/chem.201905855.


[Obstructive sleep apnea and anesthesia].
Even though the effects of surgery and anesthesia on sleep have not been completely defined yet, it is an irrefutable fact that the patients with sleep apnea could experience significant perioperative complications, in terms of common difficult airway problems, as well as prolonged emergence from anesthesia. Besides, there are strong evidences of correlation between sleep apnea and hypertension and other cardiovascular diseases. Preoperative questions about sleep, possible snoring, or excessive daytime sleepiness should become a routine part of preanesthesia evaluation, together with airway examination and thorough pulmonary and cardiovacular examination. However, the exact severity of the obstructive sleep apnea (OSA) could be precisely defined only by polysomnography. Every patient diagnosed with OSA, or with clinical suspicion of OSA, should be considered to have a difficult airway, until proven otherwise, and consequently has increased risk of anesthesia. The possible problems may arise during tracheal intubation, extubation, or with postoperative analgesia, since opioids increase the incidence of pharyngeal collapse. Whenever possible, regional anesthesia techniques should be used. On the other hand, by documenting every difficult airway management, difficult intubation or prolonged recovery, the anesthesiologists are in good position to effectively screen for OSA in population.


Energetic π-conjugated vinyl bridged triazoles: a thermally stable and insensitive heterocyclic cation.
A new family of vinyl bridge 1,1'-(ethane-5-yl)-bis(3,4-diamino-1,2,4-triazolium) salts were explored as novel structural energetic materials. These new salts were further characterized by elemental analysis, infrared and multinuclear NMR spectra. Structural confirmation of nine salts such as 4-11 and 14 was supported by single-crystal X-ray diffraction. Theoretical investigations associated with heats of formation and detonation performance were carried out by employing the Gaussian 09 program and the EXPLO5 V6.02 code, respectively. The sensitivities towards impact and friction were studied using BAM standards. According to the experimental and computational data, these salts show densities ranging from 1.61 to 1.82 g cm-3 at 298 K, good thermal stabilities (Td: 217 °C-322 °C), excellent detonation performance (P: 7809 m s-1 to 9640 m s-1, D: 24.6 GPa-33.9 GPa) and rational impact and friction sensitivities (IS: 4 J to 60 J, FS: 120 N to 360 N).


[Hypoglycemias in childhood. Pathophysiologic reflections and examples of hypoglycemias in hereditary disorders of carbohydrate metabolism].
For the understanding and interpretation of hypoglycemia it is important to know the many complex endocrine and metabolic regulations in the homoeostasis of blood glucose. Glucose-absorption, distribution and availability, glycolysis, production and utilization of glycogen as well as gluconeogenesis are important steps of this homoeostasis, and hypoglycemia always reflects a disturbance in it. When blood glucose is low the availability of energy for the brain is decreased if no alternative energy sources like lactate or ketones are provided. Hypoglycemia is more often in the neonatal period than in later childhood. The causes can be divided into different groups according to pathogenetic mechanisms. Within each group again many singular defects are known. Fructose-1,6-diphosphatase deficiency, hereditary fructose intolerance, glycogenosis type I and so called "ketotic hypoglycemia" are given as examples to elucidate special clinical and biochemical aspects of inborn errors of carbohydrate metabolism.


A prospective, longitudinal study of growth, nutrition and sedentary behaviour in young children with cerebral palsy.
Cerebral palsy is the most common cause of physical disability in childhood, occurring in one in 500 children. It is caused by a static brain lesion in the neonatal period leading to a range of activity limitations. Oral motor and swallowing dysfunction, poor nutritional status and poor growth are reported frequently in young children with cerebral palsy and may impact detrimentally on physical and cognitive development, health care utilisation, participation and quality of life in later childhood. The impact of modifiable factors (dietary intake and physical activity) on growth, nutritional status, and body composition (taking into account motor severity) in this population is poorly understood. This study aims to investigate the relationship between a range of factors - linear growth, body composition, oral motor and feeding dysfunction, dietary intake, and time spent sedentary (adjusting for motor severity) - and health outcomes, health care utilisation, participation and quality of life in young children with cerebral palsy (from corrected age of 18 months to 5 years). This prospective, longitudinal, population-based study aims to recruit a total of 240 young children with cerebral palsy born in Queensland, Australia between 1st September 2006 and 31st December 2009 (80 from each birth year). Data collection will occur at three time points for each child: 17 - 25 months corrected age, 36 +/- 1 months and 60 +/- 1 months. Outcomes to be assessed include linear growth, body weight, body composition, dietary intake, oral motor function and feeding ability, time spent sedentary, participation, medical resource use and quality of life. This protocol describes a study that will provide the first longitudinal description of the relationship between functional attainment and modifiable lifestyle factors (dietary intake and habitual time spent sedentary) and their impact on the growth, body composition and nutritional status of young children with cerebral palsy across all levels of functional ability.


Prevalence of multiple congenital contractures including arthrogryposis multiplex congenita in Alberta, Canada, and a strategy for classification and coding.
The population prevalence of multiple congenital contractures, many of which have either arthrogryposis multiplex congenita or amyoplasia congenita, ranges from 1/3300 to 1/56,000. Three other studies report a range of 1/4500 to 1/12,500. Classification and coding of these disorders in the International Classification of Diseases, tenth edition, (ICD-10) is less than satisfactory, even when augmented by the Royal College of Pediatrics and Child Health (RCPCH). expansion. The database of the Alberta Congenital Anomalies Surveillance System (ACASS) was used to review all cases (1980-2007) of the previously named disorders with special emphasis on the 1997-2007 cohort. The latter period was chosen because more complete ascertainment was likely due to the addition of terminations of pregnancy data beginning in 1997. This cohort was further analyzed into the three practical groups: I, limb only; II, limb plus non-central nervous system anomalies; and III, limb plus lethality, central nervous system anomalies, or both, with further syndrome identification in groups II and III. The ICD-10-RCPCH classification and codes were reviewed. The prevalence for multiple congenital contractures in Alberta is 1/8700 for 1980-1996 and 1/4300 for 1997-2007. Rates for the three groups were calculated. Specific diagnostic categories were found in groups II and III of 43% and 65%, respectively. Mortality is high, especially in the first month of life (45% total losses). New classification and coding systems are proposed.


[Correlation of imaging-based staging to prognosis of nasopharyngeal carcinoma: computed tomography versus magnetic resonance imaging].
Imaging results are important for clinical staging and irradiation target planning of nasopharyngeal carcinoma (NPC). This study tried to analyze the correlations of staging based on computed tomography (CT) and magnetic resonance imaging (MRI) before radiotherapy to prognosis of NPC. Clinical data of 445 pathologically confirmed NPC patients with no metastasis were analyzed. CT was performed on 230 patients before treatmentû MRI was performed on 215 patients. All patients received conventional radiotherapy, and some locally advanced patients received additional chemotherapy. Kaplan-Meier and log-rank tests were used to analyze and compare the survival rates of the two groups. Cox model was used to analyze prognostic factors. The 1-, 2-, and 3-year overall survival rates were significantly lower in CT group than in MRI group (96.9% vs. 98.6%, 90.3% vs. 94.3%, 85.3% vs. 92.3%, Chi2 =6.305, P=0.012). The 1-, 2-, and 3-year disease-free and relapse-free survival rates were also significantly lower in CT group than in MRI group (P<0.05). Univariate analysis showed that clinical stage, N stage, imaging method and chemotherapy were prognostic factors of NPC. Multivariate analysis showed that clinical stage and imaging method were independent prognostic factors of NPC. Determining target volume by MRI before radiotherapy can improve the survival rate and local control rate of NPC patients when compared with CT. Clinical stage and imaging method are independent prognostic factors of NPC patients.


The 2023 MANCTRA Acute Biliary Pancreatitis Care Bundle: A Joint Effort Between Human Knowledge and Artificial Intelligence (ChatGPT) to Optimize the Care of Patients With Acute Biliary Pancreatitis in Western Countries.
To generate an up-to-date bundle to manage acute biliary pancreatitis using an evidence-based, artificial intelligence (AI)-assisted GRADE method. A care bundle is a set of core elements of care that are distilled from the most solid evidence-based practice guidelines and recommendations. The research questions were addressed in this bundle following the PICO criteria. The working group summarized the effects of interventions with the strength of recommendation and quality of evidence applying the GRADE methodology. ChatGPT AI system was used to independently assess the quality of evidence of each element in the bundle, together with the strength of the recommendations. The seven elements of the bundle discourage antibiotic prophylaxis in patients with acute biliary pancreatitis, support the use of a full-solid diet in patients with mild to moderately-severe acute biliary pancreatitis, and recommend early enteral nutrition in patients unable to feed by mouth. The bundle states that ERCP should be performed within the first 48-72 hours of hospital admission in patients with cholangitis. Early laparoscopic cholecystectomy should be performed in patients with mild acute biliary pancreatitis. When operative intervention is needed for necrotizing pancreatitis, this should start with the endoscopic step-up approach. We have developed a new care bundle with seven key elements for managing patients with acute biliary pancreatitis. This new bundle, whose scientific strength has been increased thanks to the alliance between human knowledge and AI from the new ChatGPT software, should be introduced to emergency departments, wards, and ICUs.


Kinesin is a candidate for cross-bridging microtubules and intermediate filaments. Selective binding of kinesin to detyrosinated tubulin and vimentin.
We showed previously that stable, detyrosinated (Glu) microtubules function to localize vimentin intermediate filaments in fibroblasts (Gurland, G., and Gundersen, G. G. (1995) J. Cell Biol. 131, 1275-1290). To identify candidate proteins that mediate the Glu microtubule-vimentin interaction, we incubated microtubules with microtubule-interacting proteins and saturating levels of antibodies to Glu or tyrosinated (Tyr) tubulin. Antibodies to Glu tubulin prevented the microtubule binding of kinesin obtained from fibroblast or brain extracts more effectively than antibodies to Tyr tubulin. Scatchard plot analysis showed that kinesin heads bound to Glu microtubules with an approximately 2.8-fold higher affinity than to Tyr microtubules. Purified brain kinesin cosedimented with vimentin, but not with neurofilaments, indicating that kinesin specifically associates with vimentin without accessory molecules. Kinesin binding to vimentin was not sensitive to ATP, and kinesin heads failed to bind to vimentin. By SDS-polyacrylamide gel electrophoresis, a kinesin heavy chain of approximately 120 kDa and a light chain of approximately 64 kDa were detected in vimentin/kinesin pellets. The light chain reacted with a general kinesin light chain antibody, but not with two other antibodies that recognize the two known isoforms of kinesin light chain in brain, suggesting that the kinesin involved in binding to vimentin may be a specific one. These results demonstrate a kinesin-based mechanism for the preferential interaction of vimentin with detyrosinated microtubules.


Islamic Influence on HIV Risk and Protection Among Central Asian Male Migrant Workers in Kazakhstan.
HIV incidence is increasing in Central Asia, where migrant workers experience risks for acquiring sexually transmitted HIV. As a social and structural factor that may influence perceptions and behavior, we examine how Islam shapes HIV risk and protection. Phenomenological qualitative interviews examine religion and contexts of HIV risk among 48 male Central Asian migrant workers residing in Almaty, Kazakhstan. Men described nonvaginal sex, alcohol use, premarital sex, and extramarital sex as forbidden or frowned upon. Religious networks were unlikely to discuss HIV risks, and some men viewed religious affiliation or practices as protective. Marital practices including neke (religious marriage), polygyny, and bride kidnapping may be linked to risk. Findings suggest adhering to Islamic ideals may be protective for some men, but for others, assumptions of protection may enhance risk. HIV prevention strategies among Central Asian migrants may be strengthened by attention to religious and cultural understandings of risk and protection.


Determination of lamotrigine simultaneously with carbamazepine, carbamazepine epoxide, phenytoin, phenobarbital, and primidone in human plasma by SPME-GC-TSD.
A simple and rapid analytical method is presented for the determination of lamotrigine simultaneously with primidone, carbamazepine, carbamazepine epoxide, phenobarbital, and phenytoin in human plasma using solid-phase microextraction (SPME) and gas chromatography with thermionic specific detection. The best conditions for the SPME procedure is established as following: direct extraction on a 65-microm Carbowax-divinylbenzene fiber; 1.0 mL of a sample plasma matrix modified with 15% NaCl and 3 mL of a potassium phosphate buffer (pH 7.0); extraction temperature at 30 degrees C; and stirring at a rate of 2500 rpm for 15 min. The method shows good linearity between 0.05 and 40.0 microg/mL with regression coefficients ranging between 0.9965 and 0.9995 and a coefficient of variation of the points of the calibration curve lower than 10%. The lowest limit of quantitation for the plasma-investigated drugs varies from 0.05 to 0.20 microg/mL, according to the drug. The proposed method is sensitive enough to work into subtherapeutic and therapeutic concentrations, being that it is applied in pharmacokinetic studies and patient routine therapeutic drug monitoring.


Alpha-1,4-transglycosylation Activity of GH57 Glycogen Branching Enzymes Is Higher in the Absence of a Flexible Loop with a Conserved Tyrosine Residue.
Starch-like polymers can be created through the use of enzymatic modification with glycogen branching enzymes (GBEs). GBEs are categorized in the glycoside hydrolase (GH) family 13 and 57. Both GH13 and GH57 GBEs exhibit branching and hydrolytic activity. While GH13 GBEs are also capable of α-1,4-transglycosylation, it is yet unknown whether GH57 share this capability. Among the four crystal structures of GH57 GBEs that have been solved, a flexible loop with a conserved tyrosine was identified to play a role in the branching activity. However, it remains unclear whether this flexible loop is also involved in α-1,4-transglycosylation activity. We hypothesize that GH57 GBEs with the flexible loop and tyrosine are also capable of α-1,4-transglycosylation, similar to GH13 GBEs. The aim of the present study was to characterize the activity of GH57 GBEs to investigate a possible α-1,4-transglycosylation activity. Three GH57 GBEs were selected, one from Thermococcus kodakarensis with the flexible loop and two beta-strands; one from Thermotoga maritima, missing the flexible loop and beta-strands; and one from Meiothermus sp., missing the flexible loop but with the two beta-strands. The analysis of chain length distribution over time of modified maltooctadecaose, revealed, for the first time, that all three GH57 GBEs can generate chains longer than the substrate itself, showing that α-1,4-transglycosylation activity is generally present in GH57 GBEs.


NRTR: Neuron Reconstruction with Transformer from 3D Optical Microscopy Images.
The neuron reconstruction from raw Optical Microscopy (OM) image stacks is the basis of neuroscience. Manual annotation and semi-automatic neuron tracing algorithms are time-consuming and inefficient. Existing deep learning neuron reconstruction methods, although demonstrating exemplary performance, greatly demand complex rule-based components. Therefore, a crucial challenge is designing an end-to-end neuron reconstruction method that makes the overall framework simpler and model training easier. We propose a Neuron Reconstruction Transformer (NRTR) that, discarding the complex rule-based components, views neuron reconstruction as a direct set-prediction problem. To the best of our knowledge, NRTR is the first image-to-set deep learning model for end-to-end neuron reconstruction. The overall pipeline consists of the CNN backbone, Transformer encoder-decoder, and connectivity construction module. NRTR generates a point set representing neuron morphological characteristics for raw neuron images. The relationships among the points are established through connectivity construction. The point set is saved as a standard SWC file. In experiments using the BigNeuron and VISoR-40 datasets, NRTR achieves excellent neuron reconstruction results for comprehensive benchmarks and outperforms competitive baselines. Results of extensive experiments indicate that NRTR is effective at showing that neuron reconstruction is viewed as a set-prediction problem, which makes end-to-end model training available.


Characterisation and quantification of F8 transcripts of ten putative splice site mutations.
Mutations affecting splice sites comprise approximately 7.5 % of the known F8 gene mutations but only a few were verified at mRNA level. In the present study, 10 putative splice site mutations were characterised by mRNA analysis using reverse transcription PCR (RT-PCR). Quantitative real-time RT-PCR (RT-qPCR) and co-amplification fluorescent PCR were used in combination to quantify the amount of each of multiple F8 transcripts. All of the mutations resulted in aberrant splicing. One of them (c.6187+1del1) generated one form of F8 transcript with exon skipping, and the remaining nine mutations (c.602-6T>C, c.1752+5_1752+6insGTTAG, c.1903+5G>A, c.5219+3A>G, c.5586+3A>T, c.969A>T, c.265+4A>G, c.601+1_601+5del5 and c.1444-8_1444del9) produced multiple F8 transcripts with exon skipping, activation of cryptic splice site and/or normal splicing. Residual wild-type F8 transcripts were produced by the first six of the nine mutations with amounts of 3.9 %, 14.2 %, 5.2 %, 19.2 %, 1.8 % and 2.5 % of normal levels, respectively, which were basically consistent with coagulation phenotypes in the related patients. In comparison with the mRNA findings, software Alamut v2.3 had values in the prediction of pathogenic effects on native splice sites but was not reliable in the prediction of activation of cryptic splice sites. Our quantification of F8 transcripts may provide an alternative way to evaluate the low expression levels of residue wild-type F8 transcripts and help to explain the severity of haemophilia A caused by splicing site mutations.